Pipetting operations are often done in analysis procedures, during which liquid reagents must be assayed with great precision. Small quantities of liquid are suctioned from a reservoir and dispensed in a reactor, such as a well of a titration microplate. These pipetting operations are part of routine operations in many fields, in particular medical, chemical or pharmaceutical, and are often integrated into automatic procedures.
Naturally, it is very important to obtain a precise measurement of the volume of liquid suctioned and dispensed, but this is not sufficient. Indeed, it is still possible to encounter problems during a pipetting operation. For example, the reservoir may be empty or the end-piece of the pipette (also often called cone, point or tip) may not be entered into the liquid when the suction begins and, as a result, the pipette may suction air. The pipette may also leave the liquid before the end of the suction operation and suction air after having suctioned liquid. Furthermore, the end-piece of the pipette may also be blocked.
Consequently, in light of the high precision required in measuring the quantity of suctioned and dispensed liquid, in addition to the targeted applications, any problem occurring during a pipetting operation must be detected and reported so that no incorrect measurement may disrupt an analysis or assay.
U.S. Pat. No. 6,938,504 discloses a method for evaluating how an assay operation unfolds. It is proposed to obtain a curve that is characteristic, as a function of time, of at least one state variable of a substance present in the pipette. This characteristic curve is obtained for the entire duration of the assay operation. An analysis is next done to determine whether this characteristic curve is contained, for its entire duration, in an allowance range applied to a pre-established reference curve. Based on this analysis, a positive or negative result regarding the performance of the operation is then sent.
Such a method is interesting, but has several drawbacks. In particular, it is necessary to obtain and have in memory one or more reference curves (one for each external condition, such as the pipetted volume, the suction or dispensing speed, the type of liquid or the geometry of the tip). It is clear that the calibration of the system for detecting pipetting errors is very laborious.
Patent application WO 0188549 reveals a method for controlling the proper progression of a pipetting operation owing to the analysis of the atmospheric pressure measured in a suction tube of the device. A vacuum generator is connected by a suction tube to a pipette designed to suction and dispense liquid samples. According to the vacuum produced by the vacuum generator, the liquid is suctioned in the pipette or dispensed outside the pipette. An atmospheric pressure sensor is positioned on the suction tube connecting the vacuum generator and the pipette. Analyzing the pressure measured over a pipetting cycle makes it possible to verify the quality of the operation and detect operating anomalies.
This method has the drawback of only providing qualitative information on the pipetting operation. The measurement of the pressure of the air at the suction tube does not make it possible to determine the flow rate of the liquid flowing in the pipette or to calculate the volumes suctioned and dispensed during the pipetting operation.
The present invention aims to propose a method making it possible to avoid the aforementioned drawbacks.